The Hemophilia Growth and Development Study is a longitudinal examination of the changes in neuropsychological functioning, neurological functioning, physical growth and development, and immunologic status in otherwise healthy hemophiliac children and adolescents infected with human immunodeficiency virus (HIV) and in matched control groups of HIV negative hemophiliacs and male siblings of hemophiliacs. The significance of this study centers on the unique characteristics of the population. Participants are outside the neonatal age, being between 6 and 19 years at the time of entry to the study. They have been infected solely through blood product usage during a limited time period, predominantly between 1978 and 1984. Unlike other studies of hemophilic patients, this study addresses the problems associated with the HIV-infected growing child and his transition into puberty. Baseline data revealed that HIV positive children and adolescents were three times as likely as HIV negative participants to show deficits in attained height for age, twice as likely to have delays in sexual maturation, and more than three times as likely to exhibit certain defects in immune function. Compared to HIV negative participants, HIV positive subjects are shorter, lighter, and slower growing, and had reduced probability of sexual maturation over the studied age interval. At baseline, almost two thirds of the HIV positive group with deficits in growth also had abnormalities on brain MRI's, whereas only 25.9% of those with normal growth had abnormalities. Results of the neuropsychological test battery showed that at baseline, a greater than expected number of individuals in both HIV groups showed below average performance, and the groups as a whole had lowered performance in adaptive behavior and academic achievement, relative to IQ. After an estimated four to seven years following seroconversion, the progression of HIV brain disease in children and adolescents seroconverting past infancy may resemble the lengthy course seen in adults more than the relatively rapid course seen with vertically transmitted HIV infection. The major accomplishments of this research effort may be summarized as follows: 1) High rate of retention of study subjects. After four years, only 13% of the originally enrolled cohort nationwide has dropped out. 2) High rate of compliance with exam windows. Of those enrolled, 88% missed none or only one of the 8 followup examinations. 3) Comprehensive data bank and cells/serum bank available for further analysis and study. 4) Unique scientific observations and high publication productivity to date. As of July 1995, there have been 9 published or papers in press, 29 papers presented at scientific meetings, and 18 sets of data currently being analyzed or being prepared for publication. Expanding the effort to examine the impact of HIV on CNS functioning, the 12th followup examination included "quantitative volumetric analysis of brain MRI" for willing study participants. The relationship of HIV-related structural changes in the brain to functional impairments is poorly understood and will be investigated. Data and analyses generated to date have substantial implications on the approach to immunization of the HIV-infected child, and on public health and the control of infectious diseases. Titers of antibodies to common immunogens tend to be lower in the immunized HIV-infected child, and are not correlated with the CD4 absolute numbers. These children are underachieving neuropsychologically relative to their mental potential despite receiving modern hemophilia comprehensive care. Careful studies of educational intervention will determine the most feasible and optimal strategies for closing the functional/potential gap in these children's achievements.